argenx an example that European start-ups can become a global player

By?Guy Martin?

Last month, Belgo-Dutch autoimmune diseases specialist argenx (Nasdaq: ARGX) announced the European Commission (EC) approval of Vyvgart (efgartigimod alfa-fcab) as an add-on to standard therapy for adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

This is the third major market in which Vyvgart has been approved to treat gMG, following on from approvals in Japan and the USA, and regulatory filings are either under review or planned in a number of other geographies.

Far from looking to big pharma for help, argenx is building its own global commercialization infrastructure in North America, the European Union, the Middle East and Africa region, and in Japan.

It is a very exciting moment for the company, but this could be just the start of argenx’ arrival on pharma’s world stage – progress that marks a rare achievement for an emerging European biotech.

A major milestone

Vyvgart marks the beginning of this march, and gMG is a strong starting point. argenx is determined to follow-up regulatory approval with market access – something that has not been guaranteed for other drugs for this chronic autoimmune, neuromuscular disease. Soliris (eculizumab), from AstraZeneca (LSE: AZN) subsidiary Alexion, is licensed for gMG in Europe but it is largely unavailable in many EU member states.

Anant Murthy, general manager of argenx Europe, said that he was confident these access woes would be an issue for Vyvgart, an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G back into the blood.

“What we hear from patients is that gMG is really a devastating autoimmune disease where the body’s own antibodies attack the area between our nerves and our muscles,” Dr Murphy explained. “What that means practically for patients is incredible fatigue, weakness and, in some cases, life-threatening muscle weakness.

“When we talk to patient groups, they give us examples of how the disease affects their lives. It’s affected their ability to work – we hear often about challenges in basic care-giving, taking care of children, and so on, daily activities are significantly impaired, and we often hear about mental health challenges, social exclusion, as a result of the fatigue. On top of this, the current treatments that are used, are essentially carpet bombs of immunosuppressants, and for some patients, long-term heavy immunosuppressant and steroid use can also have a pretty devastating treatment burden.

“This approval means we can potentially transform all of that – it’s the first really targeted FcRn inhibitor that really gets at the heart of the disease, the disease-causing auto-antibodies – we knock those down.”

It is not just good news for patients and physicians – who will have another tool in their gMG armory – but is a major milestone for argenx, representing the culmination of 14 years and billions of dollars spent in R&D.

Ready to secure reimbursement

So what is the company doing to ensure swift reimbursement and access in Europe?

“Market access is really at the heart of everything we’re doing in Europe, Dr Murphy said. “Remember, argenx is a European company born in the heart of Europe, so the European market access landscape is in our DNA – we have started thinking about these challenges for quite some time and over the last few months, we’ve had several interactions with payers and healthcare authorities from different member states. We’re hopeful we can achieve really rapid agreements with payers to make efgartigimod available.”

Data showing fast, deep and clinically meaningful responses to treatment that are also durable give argenx confidence that payers will see the value of Vyvgart.

“We have some patients who, after just one cycle of treatment, were doing very well for a long time, and almost all the patients who responded, did so very quickly. So from a payer point of view, you’re not wasting time or money on a medicine that is not having an impact on patients,” Dr Murphy said.

“Equally, we designed this medicine for the dose schedule to be individualized to every patient, so depending on how a patient responds, and how they’re feeling, the physician can decide whether additional treatment cycles are necessary. For a payer, that means you’re not signing up for some chronic – every month, every three weeks, every eight weeks, whatever it is – treatment, that’s not even linked to how the patient is doing.”

argenx is taking confidence from its experience in the USA, where payers have responded very well to the data from its Phase III ADAPT study. The company’s health economic and outcomes data, documenting reductions in hospitalization and significant improvements in quality of life for patients, further demonstrate the potential for a positive impact on health systems and make the case for swift access.

'A pipeline in a product'

But Vyvgart’s potential is by no means limited to gMG and in fact could be described as a whole “pipeline in a product,” Dr Murphy said.

“Our leadership position in the biology of FcRn has allowed us to pursue R&D activities in a range of indications and we’ve got a pretty bold ambition,” he said. “We’ve said that, by the end of 2022, we’re going to move into 10 autoimmune indications including six registrational indications, where we have registrational trials, and several other proof-of-concept studies, with efgartigimod in a range of autoimmune diseases.”

Early in 2023, argenx is set to announce Phase III data in another neurology indication, this time chronic inflammatory demyelinating polyradiculoneuropathy, and later in the year, hopes to present Phase III data in its first dermatology indication, pemphigus vulgaris.

A Phase II trial is also ongoing in the dermatology indication of bullous pemphigoid, while argenx is establishing a hematology franchise and earlier this year presented positive Phase III data in primary immune thrombocytopenia (ITP) with the intravenous formulation, and the company is at a similar stage with its ITP research with a subcutaneous form.

argenx is conducting Phase II research with the same drug in lupus and membranous nephropathy alongside Zai Lab (HKG: 9688), and has partnered with IQVIA (NYSE: IQV) to conduct Phase II studies in Sjogren's syndrome, and COVID-19-induced postural orthostatic tachycardia syndrome.

Excitement at second asset

Those studies all relate to argenx' lead product but the company could have another multi-indication asset on its hands in ARGX-117, a C2 inhibitor that Dr Murphy said the firm was “really, really excited about” because of its potential across severe autoimmune indications. Research is already underway in multifocal motor neuropathy and a range of kidney indications.

“It’s already proving to be a second ‘pipeline in a product’ with those two broad indications,” Dr Murphy said.

“So across those two molecules, not even mentioning the other molecules we have in our pipeline, we’re getting close to 12 different disease areas where we could potentially have an impact on patients.”

From small to sizeable?

The potential for growth is remarkable. It is perhaps no wonder argenx’ share price has risen 16% in the past year, and is nearly 17 times higher than it was five years ago. The firm’s market capitalization is now around $21 billion.

It is rare to hear such a success story from what was a small European firm just a few short years ago and, if argenx nails the commercialization stage as well as it is managing the development phase, it will certainly not be the last that is heard of the company.